Mixed mucinous adenocarcinoma/large cell neuroendocrine carcinoma of the uterine cervix: case report and molecular characterization of a rare entity.

Mixed neuroendocrine-non-neuroendocrine carcinomas of the cervix are rare and generally aggressive diseases. They often present at an advanced stage with hematogenous or lymphatic metastases. The prognosis is poor, mostly influenced by the neuroendocrine component. Unfortunately, the rarity of the disease caused a lack of information about its pathogenesis and molecular landscape. The latest guidelines recommend a multimodal approach that usually includes radical surgery, platinum/etoposide-based chemotherapy, or chemoradiation. Here, we are presenting a case of metastatic mixed adenocarcinoma-large cell neuroendocrine carcinoma of the cervix in a 49-year-old female patient. The molecular characterization of the lesion highlighted the ubiquitous presence of human papillomavirus-18 DNA both in the adenocarcinomatous and the neuroendocrine components, suggesting a role for the virus in the pathogenesis. Moreover, a different set of mutations was detected in the two parts, thus ruling out a possible clonal evolution of the neuroendocrine component from the adenocarcinoma one. More studies are needed to clarify the molecular landscape of these rare lesions and identify putative targets for therapy.

Patients with thymomas have an increased risk of developing additional malignancies: lack of immunological surveillance?

AIMS: To assess the risk, for patients with thymoma, of developing an additional malignancy (AM). METHODS AND RESULTS: We studied 68 patients with thymomas. Based on the World Health Organization classification, the tumours were categorised as A, AB or B (B1, B2, B3) thymomas. Control populations comprised 114 patients with colorectal cancer, 108 patients with lymphoma and 123 patients with thyroid carcinoma. Patients with thymomas showed a higher risk of developing an AM (22 of 68 patients versus 11 of 114, eight of 108, and eight of 123 patients, respectively; P = 0.0002). The association between thymomas and AMs was related to the thymoma histotype, with B1, B2, B3 and AB tumours showing a higher risk of developing an AM than A thymomas (P = 0.0474). CONCLUSIONS: Patients affected by thymomas showed a significantly higher risk of developing additional malignancies than those in the control groups, and cases that exhibited a predominantly cortical component were more likely to develop other neoplasms. This may be related to the functions of cortical thymic epithelial cells in providing for T lymphocyte maturation through interaction with major histocompatibility complexes.

Lymphatic Vascularization in Prostate Adenocarcinoma: Correlation with Tumor Grade, Androgen Withdrawal and Prognosis.

BACKGROUND/AIM: The lymphatic system plays an active role in the metastatic process by directly facilitating recruitment of cancer cells into the vessels. The present study aimed to assess the lymphatic vessel area and the lymphatic vessel density in prostate adenocarcinoma and to correlate these parameters with patients prognosis and outcome. PATIENTS AND METHODS: The lymphatic vessel area and the lymphatic vessel density were evaluated using the D2-40 monoclonal antibody in 153 patients with prostate adenocarcinoma who had been treated by radical prostatectomy, in comparison to 152 non-neoplastic controls. We also estimated the lymphatic vessel area in a set of 139 patients who had undergone radical prostatectomy after neoadjuvant treatment with combined androgen blockade. RESULTS: Lymphatic vessel area was higher in periglandular than in interglandular stroma, inversely correlated with tumor differentiation (in untreated patients) and was influenced by hormonal treatment. Lymphatic vessel density was not significantly different between the non-tumoral and the high-grade prostate intraepithelial neoplasm compartment, whereas it was higher in tumoral than in non-tumoral compartments, mainly in periglandular stroma. In addition, it increased in parallel to the tumor grade progression and positively correlated with all the main prognostic factors of prostate adenocarcinoma. CONCLUSION: The evaluation of lymphatic vessel density on radical prostatectomy with positive nodes may help to discriminate those patients at higher risk of developing an aggressive disease, which may need early androgen deprivation therapy to delay the worsening of clinical disease.

Expression of Translationally Controlled Tumor Protein in Human Kidney and in Renal Cell Carcinoma.

Translationally controlled tumor protein is a multifaceted protein involved in several physiological and biological functions. Its expression in normal kidney and in renal carcinomas, once corroborated by functional data, may add elements to elucidate renal physiology and carcinogenesis. In this study, translationally controlled tumor protein expression was evaluated by quantitative real time polymerase chain reaction and western blotting, and its localization was examined by immunohistochemistry on 84 nephrectomies for cancer. In normal kidney protein expression was found in the cytoplasm of proximal and distal tubular cells, in cells of the thick segment of the loop of Henle, and in urothelial cells of the pelvis. It was also detectable in cells of renal carcinoma with different pattern of localization (membranous and cytoplasmic) depending on tumor histotype. Our data may suggest an involvement of translationally controlled tumor protein in normal physiology and carcinogenesis. However, functional in vitro and in vivo studies are needed to verify this hypothesis.

Unusual presentation of primary T-cell lymphoblastic lymphoma: description of two cases.

BACKGROUND: T-cell lymphoblastic lymphoma comprises approximately 85-90% of all lymphoblastic lymphomas. It often arises as a mediastinal mass, and with bone marrow involvement. Presentation at other sites without nodal or mediastinal localization is uncommon. CASE REPORT: We describe clinical, histologic, immunohistochemical, and molecular features of two cases of primary T-cell lymphoblastic lymphoma arising respectively in uterine corpus and testis. The tumors were composed by medium to large cells, exhibiting a diffuse pattern of growth but sometimes forming indian files or pseudo-rosettes. The neoplastic cells strongly expressed TdT and T-cell markers in both uterine corpus and testis. However, the testis case also showed aberrant expression of B-cell markers, thus molecular biology was necessary to achieve a final diagnosis. T-cell receptor gene rearrangement analysis identified a T-cell origin. CONCLUSIONS: To the best of our knowledge, only one doubtful previous case of primary uterine T-cell lymphoblastic lymphoma and no previous cases of primary testicular T-cell lymphoblastic lymphoma have been reported. Due to the morphology of neoplastic cells, a challenging differential diagnosis with all the tumors belonging to the so-called small round blue cell tumor category is mandatory. In ambiguous lineage cases, molecular biology may represent an adequate tool to confirm diagnosis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1559880973128230.

Lymphoepithelial-like carcinoma of the parotid gland: a case report and a brief review of the western literature.

BACKGROUND: Primary lymphoepithelial-like carcinoma of the parotid gland is a rare tumour with an increased incidence among Eskimos and Orientals. In these populations, it is usually associated with Epstein-Barr virus. In Western countries, salivary gland lymphoepithelial-like carcinomas are uncommon and only 14 cases have been described so far; among these, only five cases showed Epstein-Barr virus positivity. CASE REPORT: A 45-year-old woman was admitted to Siena Hospital for evaluation of a pre-existent (2 years) painless and tender submandibular mass, rapidly enlarging since two months. On physical examination, a 2.5-cm mass was found in the right parotid. It was firm, mobile and non-tender. Laboratory data were within reference range. Nuclear magnetic resonance detected a 2,5×1,5×1-cm well-circumscribed mass in the deep lobe of the right parotid. A total right paroditectomy with dissection of a satellite lymph node was performed. On the basis of morphological, immunohistochemical and molecular biology findings, a diagnosis of stage II (according to TNM7) Epstein Barr-virus positive, undifferentiated lymphoepithelial-like carcinoma of the parotid gland was made. Twenty months after surgery the patient was free of disease. CONCLUSIONS: Further studies seem to be necessary to completely elucidate the oncogenic role of Epstein Barr-virus in these tumors, which have identical morphology but different prognosis and variable presence of the virus. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1260381551000616.

Translationally controlled tumour protein (TCTP) is present in human cornea and increases in herpetic keratitis.

BACKGROUND: Translationally controlled tumour protein is a multifunctional calcium binding protein which has an important role in apoptosis, calcium levels balance and immunological response. The aim of this study was to evaluated the presence and distribution of TCTP in healthy human corneas and to identify and characterize the presence and distribution of this protein in human normal cornea. Since recent studies suggest that apoptosis, calcium levels and immunological mechanisms play a role in the pathogenesis of herpetic stromal keratitis, we studied TCTP expression in this disease. METHODS: We evaluated the expression of TCTP at both RNA messanger and protein level by using reverse transcriptase analysis, immunoblotting and immunohistochemistry in 10 healthy samples cornea: four obtained after penetrating keratoplasty and six from eyes enucleated for other pathologies. Finally, we analysed by immunohistochemistry ten paraffin-embedded samples of Herpes simplex virus keratitis collected at Siena Department of Human Pathology and Oncology: 5 had clinically quiescent disease and 5 had active corneal inflammation. RESULTS: Reverse transcriptase and immunoblotting demonstrated TCTP expression in cornea as a 22,000 Da molecular weight band corresponding to the molecular weight of this protein. Immunohistochemically, all the layers of normal corneal epithelium showed TCTP cytoplasmic expression. TCTP was, also, observed in keratocytes and in the endothelium. In Herpes simplex virus keratitis samples, strong expression of TCTP was evident in stromal cells, in the inflammatory infiltrate and in neo-vessels. CONCLUSIONS: In this preliminary study we demonstrated, for the first time, the presence of TCTP in human cornea, suggesting a potential role in the pathogenesis of herpes virus keratitis. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3306813447428149.

The alteration of lipid metabolism in Burkitt lymphoma identifies a novel marker: adipophilin.

BACKGROUND: Recent evidence suggests that lipid pathway is altered in many human tumours. In Burkitt lymphoma this is reflected by the presence of lipid droplets which are visible in the cytoplasm of neoplastic cells in cytological preparations. These vacuoles are not identifiable in biopsy section as lipids are "lost" during tissue processing. METHODS AND RESULTS: In this study we investigated the expression of genes involved in lipid metabolism, at both RNA and protein level in Burkitt lymphoma and in other B-cell aggressive lymphoma cases. Gene expression profile indicated a significant over-expression of the adipophilin gene and marked up-regulation of other genes involved in lipid metabolism in Burkitt lymphoma. These findings were confirmed by immunohistochemistry on a series od additional histological samples: 45 out of 47 BL cases showed strong adipophilin expression, while only 3 cases of the 33 of the not-Burkitt lymphoma category showed weak adipophilin expression (p<0.05). CONCLUSIONS: Our preliminary results suggest that lipid metabolism is altered in BL, and this leads to the accumulation of lipid vacuoles. These vacuoles may be specifically recognized by a monoclonal antibody against adipophilin, which may therefore be a useful marker for Burkitt lymphoma because of its peculiar expression pattern. Moreover this peptide might represent an interesting candidate for interventional strategies.